Method of maintaining constant arterial PCO2 and measurement of anatomic and alveolar dead space

ABSTRACT

A method to maintain isocapnia for a subject. A fresh gas is provided to the subject when the subject breathes at a rate less than or equal to the fresh gas flowing to the subject. The fresh gas flow equal to a baseline minute ventilation minus a dead space gas ventilation of the subject contains a physiological insignificant amount of CO 2 . An additional reserve gas is provided to the subject when the subject breathes at a rate more than the fresh gas flowing to the subject. The reserve gas has a partial pressure of carbon dioxide equal to an arterial partial pressure of carbon dioxide of the subject. A breathing circuit is applied to the method to maintain isocapnia for a subject. The breathing circuit has an exit port, a non-rebreathing valve, a source of fresh gas, a fresh gas reservoir and a reserve gas supply.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This Application claims priority to Canadian Application SerialNo. 2,346,517 filed May 4, 2001.

STATEMENT RE FEDERALLY SPONSORED RESEARCH/DEVELOPMENT

[0002] (Not applicable)

BACKGROUND OF INVENTION

[0003] The present invention relates to a method to maintain isocapniawhen breathing exceeds baseline breathing and a circuit therefor.Preferably, the circuit includes a non-rebreathing valve, a source offresh gas, a fresh gas reservoir and a source of gas to be inhaled whenminute ventilation exceeds fresh gas flow. Preferably the flow of thefresh gas is equal to minute ventilation minus anatomic dead space. Anyadditional inhaled gas exceeding fresh gas flow has a partial pressureof CO₂ equal to the partial pressure of CO₂ of arterial blood.

[0004] Venous blood returns to the heart from the muscles and organspartially depleted of oxygen (O₂) and a full complement of carbondioxide (CO₂). Blood from various parts of the body is mixed in theheart (mixed venous blood) and pumped into the lungs via the pulmonaryartery. In the lungs, the blood vessels break up into a net of smallvessels surrounding tiny lung sacs (alveoli). The vessels surroundingthe alveoli provide a large surface area for the exchange of gases bydiffusion along their concentration gradients. After a breath of air isinhaled into the lungs, it dilutes the CO₂ that remains in the alveoliat the end of exhalation. A concentration gradient is then establishedbetween the partial pressure of CO₂ (PCO₂) in the mixed venous blood(PvCO₂) arriving at the alveoli and the alveolar PCO₂. The CO₂ diffusesinto the alveoli from the mixed venous blood from the beginning ofinspiration (at which time the concentration gradient for CO₂ isestablished) until an equilibrium is reached between the PCO₂ in bloodfrom the pulmonary artery and the PCO₂ in the alveolae at some timeduring breath. The blood then returns to the heart via the pulmonaryveins and is pumped into the arterial system by the left ventricle ofthe heart. The PCO₂ in the arterial blood, termed arterial PCO₂ (PaCO₂)is then the same as was in equilibrium with the alveoli. When thesubject exhales, the end of his exhalation is considered to have comefrom the alveoli and thus reflects the equilibrium CO₂ concentrationbetween the capillaries and the alveoli. The PCO₂ in this gas is theend-tidal PCO₂ (P_(ET)CO₂). The arterial blood also has a PCO₂ equal tothe PCO₂ at equilibrium between the capillaries and alveoli.

[0005] With each exhaled breath some CO₂ is eliminated and with eachinhalation, fresh air containing no CO₂ is inhaled and dilutes theresidual equilibrated alveolar PCO₂, establishing a new gradient for CO₂to diffuse out of the mixed venous blood into the alveoli. The rate ofbreathing, or ventilation (V_(E)), usually expressed in L/min, isexactly that required to eliminate the CO₂ brought to the lungs andestablish an equilibrium P_(ET)CO₂ and PaCO₂ of approximately 40 mmHg(in normal humans). When one produces more CO₂ (e.g. as a result offever or exercise) more CO₂ is carried to the lungs and one then has tobreathe harder to wash out the extra CO₂ from the alveoli, and thusmaintain the same equilibrium PaCO₂. But if the CO₂ production staysnormal, and one hyperventilates, then excess CO₂ is washed out of thealveoli and the PaCO₂ falls.

[0006] It is important to note that not all V_(E) contributes toelimination of CO₂. The explanation for this is with reference to theschematic in the lung depicted in FIG. 10. The lung contains two regionsthat do not participate in gas equilibration with the blood. The firstcomprises the set of conducting airways (trachea and bronchi) 100 thatact as pipes directing the gas to gas exchanging areas. As theseconducting airways do not participate in gas exchange they are termedanatomic dead space 102 and the portion of V_(E) ventilating theanatomic dead space is termed anatomic dead space ventilation (V_(Dan))The same volume of inhaled gas resides in the anatomic dead space oneach breath. The first gas that is exhaled comes from the anatomic deadspace and thus did not undergo gas exchange and therefore will have agas composition similar to the inhaled gas. The second area where thereis no equilibration with the blood comprises the set of alveoli 103 thathave lost their blood supply; they are termed alveolar dead space 104.The portion of V_(E) ventilating the alveolar dead space is termedalveolar dead space ventilation (V_(Dalv)). Gas is distributed toalveolar dead space in proportion to their number relative to that ofnormal alveoli (normal alveoli being those that have blood vessels andparticipate in gas exchange with blood). That portion of V_(E) that goesto well perfused alveoli and participates in gas exchange is called thealveolar ventilation (V_(A)). In FIG. 10, the numeral references 105 and106 indicate the pulmonary capillary and the red blood cell,respectively.

[0007] Prior art circuits used to prevent decrease in PCO₂ resultingfrom increased ventilation, by means of rebreathing of previouslyexhaled gas are described according to the location of the fresh gasinlet, reservoir and pressure relief valve with respect to the patient.They have been classified by Mapleson and are described in Dorsch andDorsch pg 168.

[0008] Mapleson A

[0009] The circuit comprises a pressure relief valve nearest to thepatient, a tubular reservoir and fresh inlet distal to the patient. Inthis circuit, on expiration, dead space gas is retained in the circuit,and after the reservoir becomes full, alveolar gas is lost through therelief valve. Dead space gas is therefore preferentially rebreathed.Dead space gas has a PCO₂ much less than PaCO₂. This is less effectivein maintaining PCO₂ than rebreathing alveolar gas, as occurs with thecircuit of the present invention.

[0010] Mapleson B and C

[0011] The circuit includes a relief valve nearest the patient, and areservoir with a fresh gas inlet at the near patient port. As withMapleson A dead space gas is preferentially rebreathed when minuteventilation exceeds fresh gas flow. In addition, if minute ventilationis temporarily less than fresh gas flow, fresh gas is lost from thecircuit due to the proximity of the fresh gas inlet to the relief valve.Under these conditions, when ventilation once again increases, there isno compensation for transient decrease in ventilation as the loss offresh gas will prevent a compensatory decrease in PCO₂.

[0012] Mapleson D and E

[0013] Mapleson D consists of a circuit where fresh gas flow enters nearthe patient port, and gas exits from a pressure relief valve separatedfrom the patient port by a length of reservoir tubing. Mapleson E issimilar except it has no pressure relief valve allowing the gas tosimply exit from an opening in the reservoir tubing. In both circuits,fresh gas is lost without being first breathed. The volume of gas lostwithout being breathed at a given fresh flow is dependent on the patternof breathing and the total minute ventilation. Thus the alveolarventilation and the PCO₂ level are also dependent on the pattern ofbreathing and minute ventilation. Fresh gas is lost because duringexpiration, fresh gas mixes with expired gas and escapes with it fromthe exit port of the circuit. With the present invention, all of thefresh gas is breathed by the subject.

[0014] There are many different possible configurations of fresh gasinlet, relief valve, reservoir bag and CO₂ absorber (see Dorsch andDorsch, pg. 205-207). In all configurations, a mixture of expired gasesenters the reservoir bag, and therefore rebreathed gas consists ofcombined dead space gas and alveolar gas. This is less efficient inmaintaining PCO₂ constant than rebreathing alveolar gas preferentiallyas occurs with our circuit, especially at small increments of V abovethe fresh gas flow.

BRIEF SUMMARY OF THE INVENTION

[0015] The present invention comprises a method and a circuit thatmaintains a constant PCO₂ More particularly, the present inventionmaintains a constant PCO₂ by:

[0016] 1) setting FGF equal to the baseline minute ventilation less theanatomical dead space ventilation (V_(Dan)); and

[0017] 2) establishing PrgCO₂ being equal to the PaCO₂ rather than thePvCO₂ to increase accuracy of the methods herein disclosed.

[0018] In the present invention, when minute ventilation is temporarilyless than fresh gas flow, no fresh gas is lost from the circuit.Instead, the reservoir acts as a buffer to store extra fresh gas. Whenventilation increases once more, the subject breathing the accumulatedfresh gas allows PCO₂ to return to the previous level.

[0019] A circuit to maintain isocapnia is also provided by theinvention. The circuit includes a non rebreathing valve, a source offresh gas, a fresh gas reservoir and a source of gas to be inhaled whenminute ventilation exceeds fresh gas flow. Preferably, the flow of freshgas is equal to minute ventilation minus anatomic dead space. Anyadditional inhaled gas exceeding fresh gas flow has a partial pressureof CO₂ equal to the partial pressure of CO₂ of arterial blood.

[0020] The invention further provides a method of measuring anatomicaland/or alveolar dead space ventilation by using a breathing circuitconsisting of a non rebreathing valve, a source of fresh gas, a freshgas reservoir and a source of gas with a partial pressure of CO₂substantially equal to that of arterial blood.

[0021] In one embodiment of the invention, the non-rebreathing circuitcomprises an exit port, a non-rebreathing valve, a source of fresh gas,a fresh gas reservoir, and a reservoir gas supply. From the exit port,gases are supplied from the circuit to the patient. The non-rebreathingvalve has a one-way valve permitting gases to be delivered to the exitport to the patient, but prevents gases from passing into the circuit.The source of fresh gas may be oxygen, air or the like excluding CO₂(air containing physiologically insignificant amount of CO₂) and is incommunication with the non-rebreathing valve to be delivered to thepatient. The fresh gas reservoir is in communication with the source offresh gas flow for receiving excess fresh gas not breathed by thepatient from the source of fresh gas and for storage thereof, wherein asthe patient breathes gas from the source of fresh gas flow and from thefresh gas reservoir are available depending on the minute ventilationlevel. The reserve gas supply contains CO₂ and other gases (usuallyoxygen) preferably having a partial pressure of the CO₂ approximatelyequal to the partial pressure of CO₂ in the arterial blood of thepatient. The reserve gas supply is delivered to the non-rebreathingvalve to make up that amount of gas required by the patient forbreathing that is not fulfilled from the gases delivered from the sourceof fresh gas flow and the fresh gas reservoir. The source of gas, thefresh gas reservoir and the reserve gas supply are disposed on the sideof the non-breathing valve remote from the exit port.

[0022] Preferably, a pressure relief valve is provided in the circuit incommunication with the fresh gas reservoir in the event that the freshgas reservoir overfills with gas so that the fresh gas reservoir doesnot break, rupture or become damaged in any way.

[0023] The reserve gas supply preferably includes a demand valveregulator. When additional gas is required, the demand valve regulatoropens the communication of the reserve gas supply to the non-rebreathingvalve for delivery of the gas thereto. When additional gas is notrequired, the demand valve regulator is closed and only fresh gas flowsfrom the source of fresh gas and from the fresh gas reservoir to thenon-rebreathing valve. The source of fresh gas is set to supply freshgas (non-CO₂-containing gas) at a rate equal to desired alveolarventilation for the elimination of CO₂, that is, the baseline minuteventilation minus anatomical dead space.

[0024] The basic concept of the present invention is when breathingincreases, flow of fresh gas (inspired PCO₂=0) from the fresh gas flowcontributing to elimination of CO₂ is kept constant, and equal to thebaseline minute ventilation minus anatomical dead space. The remainderof the gas inhaled by the subject (from the reserve gas supply) has aPCO₂ equal to that of arterial blood, resulting in the alveolar PCO₂stabilizing at the arterial PCO₂ level regardless of the level ofventilation as long as minute ventilation minus anatomical dead space isgreater than the fresh gas flow. In the event that the desired PaCO₂ isa particular value, which may be higher or lower than the initial PaCO₂of the subject, then the PCO₂ having an adjustable feature of thereserve gas may simply be set equal to the desired PaCO₂. If the PaCO₂is specifically desired to remain equal to the initial PaCO₂ of thesubject, then the PaCO₂ can be measured by obtaining a sample ofarterial blood from any artery, and the PCO₂ of the reserve gas setequal to this valve. Alternatively, an estimation of the PaCO₂ can bemade from P_(ET)CO₂. P_(ET)CO₂ is determined by measuring the PCO₂ ofexpired breath using a capnograph usually present or easily available inmedical and research facilities to persons skilled in the art.

[0025] In effect, the present invention passively causes the amount ofCO₂ breathed in by the patient to be proportional to the amount of totalbreathing, thereby preventing any perturbation of the arterial PCO₂.This is unlike prior art servo-controllers which always attempt tocompensate for changes. Persons skilled in the art, however, may chooseto automate the circuit by using a servo-controller or computer tomonitor minute ventilation levels and deliver inspired gas with theconcentrations of CO₂ substantially equal to that of those from freshgas and reserve gas were the gases mixed together.

[0026] The non-rebreathing circuit provided by the present invention canalso be used to enable a patient to recover more quickly from, and tohasten the recovery of the patient after vapor anaestheticadministration, or poisoning with carbon monoxide, methanol, ethanol, orother volatile hydrocarbons.

[0027] According to another aspect of the invention, a method oftreatment of an animal or person is provided. The method comprisesdelivering to a patient gases which do not contain CO₂ at a specificrate, and gases containing CO₂ to maintain the same PCO₂ in the patient,at the rate of ventilation of the patient which exceeds the rate ofadministration of the gases which do not contain CO₂ independent of therate of ventilation.

[0028] The circuit and method of treatment can also be used for anycircumstance where it is desirable to dissociate the minute ventilationfrom elimination of carbon dioxide such as respiratory muscle training,investigation of the role of pulmonary stretch receptors,tracheobronchial tone, expand the lung to prevent atelectasis, exercise,and control of respiration and other uses as would be understood bythose skilled in the art.

[0029] The circuit and method of treatment of the present invention mayalso be used by deep sea divers and astronauts to eliminate nitrogenfrom the body. It can also be used to treat carbon monoxide poisoningunder norma baric or hyper baric conditions. In this case, the fresh gaswould contain a higher concentration of oxygen than ambient air, forexample, 100% O₂, and the reserve gas will contain approximately 5.6%CO₂ and a high concentration of oxygen, for example, 94% of O₂.

[0030] In another embodiment of the invention, a method of controllingPCO₂ in a patient at a predetermined desired level is providedcomprising a breathing circuit which is capable of organizing exhaledgas so as to be preferentially inhaled during re-breathing whennecessary by providing alveolar gas for re-breathing in preference todead space gas. The preferred circuit in effecting this method includesa breathing port for inhaling and exhaling gas, a bifurcated conduitadjacent to the port. The bifurcated conduit has a first and a secondconduit branches. The first conduit has a fresh gas inlet and a checkvalve allowing the passage of inhaled fresh gas to the port but closingduring exhalation. The second conduit branch includes a check valvewhich allows passage of exhaled gas through the check valve but preventsflow back to the port. A fresh gas reservoir is located at the terminusof the first conduit branch, while an exhaled gas reservoir is locatedat the terminus of the second conduit branch. An interconnecting conduithaving a check valve therein is located between the first and the secondconduit branches to result in the fresh flow gas in the circuit equal tobaseline minute ventilation minus ventilation of anatomic dead space forthe patient. In the exhaled gas reservoir, the exhaled gas is preferablydisposed nearest the open end thereof, and the alveolar gas is locatedproximate the end of the reservoir nearest the terminus of the secondconduit branch, so that the shortfall differential of PCO₂ is made ofalveolar gas being preferentially rebreathed, thereby preventing achange in the PCO₂ level of alveolar gas despite the increased minuteventilation.

[0031] It is important to set up the fresh gas flow to be baselineminute ventilation minus anatomic dead space ventilation. In this way,once it is desired to increase the minute ventilation, a slight negativepressure will exist in the interconnecting conduit during inhalation,opening its check valve and allowing further breathing beyond the normallevel of ventilation to be supplied by previously exhaled gas.

[0032] The present invention also provides a method of enhancing theresults of a diagnostic procedure or medical treatment. A circuit whichis capable of organizing exhaled gas so as to provide to the patientpreferential rebreathing of alveolar gas in preference to dead space gasis provided. The patient is ventilated when a rate greater than thefresh gas flow is desired, and when hypercapnia is desired to induce.The fresh gas flow is passively decreased to provide a correspondingincrease in rebreathed gas. The hypercapnia is continuously induceduntil the diagnostic or medical procedure is complete. Examples of themedical procedure includes MRI, radiation treatment or the like.

[0033] The present invention can also be applied to treat or assist apatient, preferably human, during a traumatic event characterized byhyperventilation. A breathing circuit in which alveolar ventilation isequal to the fresh gas flow and increases in alveolar ventilation withincreases in minute ventilation is prevented, is provided. The circuitis capable of organizing exhaled gas provided to the patient andpreferential rebreathing alveolar gas in preference to dead space gasfollowing ventilating the patient at a rate of normal minuteventilation, preferably approximately 5 L per minute. When desired,hypercapnia is induced to increase arterial PCO₂ and prevent the PCO₂level of arterial blood from dropping. The normocapnia is maintaineddespite the ventilation is increased until the traumatichyperventilation is complete. As a result, the effects ofhyperventilation experienced during the traumatic event are minimized.This can be applied when a mother is in labor and becomes light headedor when the baby during the delivery is effected with the oxygendelivery to its brain being decreased as a result of contraction of theblood vessels in the placenta and fetal brain. A list of circumstancesin which the method enhancing the diagnostic procedure results or theexperience of the traumatic even are listed below.

[0034] Applications of the method and circuit includes:

[0035] 1) Maintenance of constant PCO₂ and inducing changes in PCO₂during MRI.

[0036] 2) Inducing and/or marinating increased PCO₂:

[0037] a) to prevent or treat shivering and tremors during labor,post-anesthesia, hypothermia, and certain other pathological states;

[0038] b) to treat fetal distress due to asphyxia;

[0039] c) to induce cerebral vasodilatation, prevent cerebral vasospasm,and provide cerebral protection following subarachnoid hemorrhagecerebral trauma and other pathological states;

[0040] d) to increase tissue perfusion in tissues containing cancerouscells to increase their sensitivity to ionizing radiation and deliveryof chemotherapeutic agents;

[0041] e) to aid in radio diagnostic procedures by providing contrastbetween tissues with normal and abnormal vascular response; and

[0042] f) protection of various organs such as the lung, kidney andbrain during states of multi-organ failure.

[0043] 3) Prevention of hypocapnia with O₂ therapy, especially inpregnant patients.

[0044] 4) Other applications where O₂ therapy is desired and it isimportant to prevent the accompanying drop in PCO₂.

[0045] By carrying out the above method and preferably with the abovecircuit, an improved method of creating MRI images is disclosed tomaintain a constant PCO₂ and induce changes in that PCO₂ level duringthe MRI procedure in order to facilitate improvement in the quality ofthe images being obtained. The prior art Mapleson D and E circuitspredictably may work with the method of the present invention as well asa standard circuit with the carbon dioxide filter bypassed or removed;however fresh gas will be wasted and the efficiency would be reduced.

[0046] A method of delivering to a patient, preferably human, inhaleddrugs such as gases, vapors or suspensions of solid particles, particlesor droplets, for example, nitric oxide, anesthetic vapors,bronchodilators or the like, using the above circuit to increase theefficiency of delivery allows the quantification of the exact dose.

[0047] A method of delivering to a patient, preferably human, pureoxygen is provided. The circuit described above increases the efficiencyof delivery because all the fresh gas is inhaled by the patient, or todeliver the oxygen to the patient in a more predictable way, allowingthe delivery of a precise concentration of oxygen.

[0048] When minute ventilation minus anatomical dead space ventilationis greater than or equal to fresh gas flow, the above circuit preventsloss of fresh gas and ensures that the patient receives all the freshgas independent of the pattern of breathing since fresh gas alone entersthe fresh gas reservoir, and exhaled gas enters its own separatereservoir. The fresh gas reservoir bag is large enough to store freshgas for 5-10 seconds or more of reduced ventilation or total apnea,ensuring that even under these circumstances fresh gas will not be lost.The preferred circuit prevents rebreathing at a minute ventilation equalto the fresh gas flow because the check valve in the interconnectingconduit does not open to allow rebreathing of previously exhaled gasunless a negative pressure exist on the inspiratory side of the conduitof the circuit. Also, when minute ventilation exceeds the fresh gasflow, a negative pressure occurs in the inspiratory conduit, opening theconduit's check valve. The circuit provides that after the check valveopens, alveolar gas is rebreathed in preference to dead space gasbecause the interconnecting conduit is located such that exhaledalveolar gas will be closest to it and dead space gas will be furtherfrom it. When the fresh gas flow is equal to VE−V_(Dan) the volume ofrebreathed gas will ventilate the anatomical dead space only, leavingthe alveolar ventilation unchanged. The exhaled gas reservoir ispreferably sized at 3 L which is well in excess of the volume of anindividual's breath, therefore it is unlikely that the patient shall beable to breathe any room air entering via the opening at the end of theexhaled gas reservoir.

[0049] The basic approach of preventing a decrease in PCO₂ withincreased ventilation is similar to that of the non-rebreathing system.In brief, only the fresh gas contributes to alveolar ventilation (V_(A))which establishes the gradient for CO₂ elimination. All gas breathed inexcess of the fresh gas entering the circuit, or the fresh gas flow, isrebreathed gas. The terminal part of the exhaled gas contains gas thathas been in equilibrium with arterial blood and hence has a PCO₂substantially equal to arterial blood. The Fisher (WO98/41266) patentteaches that the closer PCO₂ in the inhaled gas to PvCO₂, the less theeffect on CO₂ elimination. Yet, it would not maintain a constant PaCO₂as V_(E) increases. The present invention discloses that the greater theventilation of gas with a PCO₂ equal to PvCO₂, the closer the PaCO₂ getsto PvCO₂. The present invention also discloses that when PCO₂ of inhaledgas is substantially equal to PaCO₂, increased ventilation will not tendto change the PaCO₂. Since the terminal part of the exhaled gas containsgas that has been in equilibrium with arterial blood and hence has aPCO₂ substantially equal to arterial blood, the PaCO₂ will be unchangedregardless of the extent of rebreathing.

[0050] With the use of the circuit of the present invention:

[0051] 1. All of the fresh gas is inhaled by the subject when minuteventilation minus anatomical dead space is equal to or exceeds fresh gasflow.

[0052] 2. The “alveolar gas” is preferentially rebreathed when minuteventilation minus anatomical dead space exceeds the fresh gas flow.

[0053] 3. When minute ventilation minus anatomical dead space is equalto or greater than fresh gas flow, all the fresh gas contributes toalveolar ventilation.

[0054] In another embodiment of the invention, a method of establishinga constant flow of fresh gas in the form of atmospheric air forced as aresult of breathing efforts by the patient, but independent of theextent of ventilation, is provided. The flow is delivered into abreathing circuit such as that taught by Fisher et al.,(non-rebreathing) designed to keep the PCO₂ constant by providingexpired gas to be inhaled when the minute ventilation exceeds the flowof fresh gas. Furthermore, there is provided a compact expired gasreservoir capable of organizing exhaled gas so as to be preferentiallyinhaled during rebreathing when necessary by providing alveolar gas forre-breathing in preference to dead space gas. The preferred circuit ineffecting the above-mentioned method includes a breathing port forinhaling and exhaling gas, a bifurcated conduit adjacent to the port insubstantially a Y-shape. The bifurcated conduit has a first and a secondconduit branches. The first conduit has an atmospheric air inlet theflow through which is controlled by a resistance for example that beingprovided by a length of tubing, and a check valve allowing the passageof inhaled atmospheric air to the port but closing during exhalation.The second conduit branch includes a check valve which allows passage ofexhaled gas through the check valve but prevents flow back to the port.An atmospheric air aspirator (AAA) is located at the terminus of thefirst conduit branch, while an exhaled gas reservoir of about 3 L incapacity is located at the terminus of the second conduit branch. TheAAA comprises a collapsible container tending to recoil to openposition. An interconnecting conduit having a check valve therein islocated between the first and the second conduit branches. When minuteventilation minus anatomic dead space ventilation is equal to the rateof atmospheric air aspirated into the circuit, for example, 4 L perminute, atmospheric air enters the breathing port from the first conduitbranch at a predetermined rate and preferably 4 L per minute. Meanwhile,the exhaled gas at a rate of 4 L per minute travels town to the exhaledgas reservoir. When it is desirable for the minute ventilation to exceedthe fresh gas flow, for example, 4 L per minute, the patient will inhaleexpired gas retained in the expired gas reservoir through theinterconnecting conduit at a rate making up the shortfall of theatmospheric air.

[0055] While setting the fresh gas flow to maintain a desired PCO₂, itis important to set up the atmospheric air aspirator be allowed to firstbe depleted of gas until it just empties at the end of the inhalationcycle. In this way, once it is desired to increase the minuteventilation, the increased breathing effort required to do so willfurther decrease the sub-atmospheric pressure in the first conduitbranch, being the inspiratory limb, and open the check valve in theinterconnecting conduit to allow further breathing of gas beyond thelevel of ventilation supplied by the volume of atmospheric air aspiratedinto the circuit during the entire breathing cycle.

[0056] The circuit of the present invention is particularly applicablewhen atmospheric air is a suitable form of fresh gas and when it isinconvenient or impossible to access a source of compressed gas or airpump to provide the fresh gas flow. During mountain climbing or workingat high altitude, some people tend to increase their minute ventilationto an extent greater than that required to optimize the alveolar oxygenconcentration. This will result in an excessive decrease in PCO₂ whichwill in turn result in an excessive decrease in flood flow and henceoxygen delivery to the brain. By using the above circuit at highaltitude a limit can be put on the extent of decrease in PCO₂ and thusmaintain the oxygen delivery to the brain in the optimal range.

[0057] During resuscitation of an asphyxiated newborn or an adultsuffering a cardiac arrest, the blood flow through the lungs isremarkably slow during resuscitation attempts. Even normal rates ofventilation may result an excessive elimination of CO₂ from the blood.As the blood reaches brain, the low PCO₂ may constrict the blood vesselsand limit the potential blood flow to the ischemic brain. By attachingthe isocapnia circuit provided by the invention to the gas inlet port ofa resuscitation bag and diverting all expiratory gas to the expiratorygas reservoir bag, the decrease of PCO₂ would be limited.

[0058] The isocapnia circuit of the present invention can be applied toenhance the results of a diagnostic procedure or a medical treatment byproviding a circuit without a source of forced gas flow and beingcapable of organizing exhaled gas. With the circuit, preferentialrebreathing of alveolar gas in preference to dead space gas is providedwhen the patient is ventilating at a rate greater than the rate ofatmospheric air aspirated, and when inducing hypercapnia is desired. Bydecreasing the rate of aspirated atmospheric air, a correspondingincrease in rebreathed gas is passively provided to prevent the PCO₂level of arterial blood from dropping despite increase in minuteventilation. The step of inducing hypercapnia is continued until thediagnostic or medical therapeutic procedure is complete. The results ofthe diagnostic or medical procedure are thus enhanced by carrying outthe method in relation to the results of the procedure had the methodnot been carried out. Examples of such procedures include MRI orpreventing spasm of brain vessels after brain hemorrhage, radiationtreatments or the like.

[0059] The present invention can also be applied to treat or assist apatient, preferably human, during a traumatic event characterized byhyperventilation. A circuit that does not require a source of forced gasflow, in which alveolar ventilation is equal to the rate of atmosphericair aspirated and increases in alveolar ventilation with increases inminute ventilation is prevented, is provided. For example, the isocapniacircuit as described above, is capable of organizing exhaled gasprovided to the patient preferential rebreathing alveolar gas inpreference to dead space gas following ventilating the patient at a rateof normal minute ventilation, preferably approximately 5 L per minute.When desired, hypercapnia is induced to increase arterial PCO₂ andprevent the PCO₂ level of arterial blood from dropping. The normocapniais maintained despite the ventilation being increased until thetraumatic hyperventilation is complete. As a result, the effects ofhyperventilation experienced during the traumatic event are minimized.This can be applied when a mother is in labor and becomes light headedor the baby during the delivery is effected with the oxygen delivery toits brain being decreased as a result of contraction of the bloodvessels in the placenta and fetal brain. A list of circumstances inwhich the method enhancing the diagnostic procedure results or theexperience of the traumatic even are listed below.

[0060] Applications of the method and circuit includes:

[0061] 1) Maintenance of constant PCO₂ and inducing changes in PCO₂during MRI.

[0062] 2) Inducing and/or marinating increased PCO₂:

[0063] a) to prevent or treat shivering and tremors during labor,post-anesthesia, hypothermia, and certain other pathological states;

[0064] b) to treat fetal distress due to asphyxia;

[0065] c) to induce cerebral vasodilatation, prevent cerebral vasospasm,and provide cerebral protection following subarachnoid hemorrhagecerebral trauma and other pathological states;

[0066] d) to increase tissue perfusion in tissues containing cancerouscells to increase their sensitivity to ionizing radiation and deliveryof chemotherapeutic agents;

[0067] e) to aid in radio diagnostic procedures by providing contrastbetween tissues with normal and abnormal vascular response; and

[0068] f) protection of various organs such as the lung, kidney andbrain during states of multi-organ failure.

[0069] 3) Prevention of hypocapnia with O₂ therapy, especially inpregnant patients.

[0070] 4) Other applications where O₂ therapy is desired and it isimportant to prevent the accompanying drop in PCO₂.

[0071] When minute ventilation is greater than or equal to the rate ofatmospheric air aspirated, the above-mentioned preferred circuit ensuresthat the patient receives all the atmospheric air aspirated into thecircuit, independent of the pattern of breathing; since atmospheric airalone enters the fresh gas reservoir and exhaled gas enters its ownseparate reservoir and all the aspirated air is delivered to the patientduring inhalation before rebreathed exhaled gas. The atmospheric airaspirator preferably large enough not to fill to capacity duringprolonged exhalation, when the total minute ventilation exceeds the rateof atmospheric air aspiration ensuring that under these circumstancesatmospheric air continues to enter the circuit uninterrupted duringexhalation. The preferred circuit prevents rebreathing at a minuteventilation equal to the rate of air being aspirated into theatmospheric air aspirator because the check valve in the interconnectingconduit does not open to allow rebreathing of previously exhaled gasunless a sub-atmospheric pressure less than that generated by the recoilof the aspirator exists on the inspiratory side of the conduit of thecircuit. The circuit provides that after the check valve opens, alveolargas is rebreathed in preference to dead space gas because theinterconnecting conduit is located such that exhaled alveolar gascontained in the tube conducting the expired gas into the expiratoryreservoir bag will be closest to it and dead space gas will be mixedwith other exhaled gases in the reservoir bag. In the preferredembodiment, the exhaled gas reservoir is preferably sized at about 3 Lwhich is well excess of the volume of an individual's breath. When thepatient inhales gas from the reservoir bag, the reservoir bag collapsesto displace the volume of gas extracted from the bag, minimizing thevolume of atmospheric air entering the bag.

[0072] The basic approach of the present invention to prevent a decreasein PCO₂ with increase ventilation is to arrange that the fresh gasenters, the circuit at a rate equal to the desired minute ventilationminus anatomic dead space ventilation. In brief, breathing only freshgas contributes to alveolar ventilation (V_(A)) which establishes thegradient for CO₂ elimination. All gas breathed in excess of the freshgas entering the circuit, or the fresh gas flow, is rebreathed gas. Thecloser the partial pressure of carbon dioxide in the inhaled gas to thatof arterial blood, the less the effect on CO₂ elimination. Withincreased levels of ventilation, greater volumes of previously exhaledgas are breathed. The rebreathed gas has a PCO₂ substantially equal tothat of arterial blood, thus contributing little if anything to alveolarventilation, and allowing the P_(ET)CO₂ and PaCO₂ to change little.

[0073] Further, if the fresh gas flow is equal to the minute ventilationminus the anatomic dead space ventilation, when minute ventilation isequal to or exceeds the rate of atmospheric air aspirated into thecircuit, then all of the delivered fresh gas remains constant and equalto the resting alveolar ventilation. The “alveolar gas” ispreferentially rebreathed when minute ventilation exceeds the fresh gasflow. These, as well as other features of the present invention willbecome more evident upon reference to the drawings and detaileddescription of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0074]FIG. 1 illustrates schematically the nature of the simplenon-rebreathing circuit and components which enable the patient torecover more quickly from vapor anaesthetics or other volatile agents.The device enables the arterial or end-tidal PCO₂ to remain relativelyconstant despite increase in minute ventilation which thereby permitsfaster elimination of the vapor anaesthetic or other volatile compounds;

[0075]FIG. 2 illustrates schematically portions of a standard circleanaesthetic;

[0076]FIG. 3 illustrates schematically the simple non-rebreathingcircuit in one embodiment added to portions of the circle anaestheticcircuit shown schematically in FIG. 2, illustrating modifications of thecircuit shown schematically in FIG. 1 for use with the circuit shown inFIG. 2;

[0077]FIG. 4A illustrates the structure shown in FIG. 3 combined withthe structure shown in FIG. 2;

[0078]FIGS. 4B and 4C illustrate schematically close up portions of oneportion of the structure shown in FIG. 4A in different positions;

[0079]FIG. 5 depicts schematic representations of a lung atprogressively increasing ventilations (A-D). Gas in the alveolarcompartment of the lung participates in gas exchange, and thus cancontribute to the elimination of CO₂, whereas gas in the anatomical deadspace does not contribute to gas exchange. The hatched area indicatesfresh gas; the stippled area indicates reserve gas;

[0080]FIG. 6 illustrates a mathematical model used to calculate PaCO₂ asa function of minute ventilation;

[0081]FIG. 7 illustrates schematically the nature of the simplebreathing circuit and components enabling the PCO₂ to remain constantdespite in crease in minute ventilation;

[0082]FIG. 8 illustrates a graph of how FGF flow may be slowly decreasedaffecting P_(ET)CO₂ exponentially in time;

[0083]FIG. 9 is a schematic view of the portable circuit of theinvention; and

[0084]FIG. 10 is a schematic view of the lungs illustrating anatomicaldead space in relation to alveolar dead space.

DETAILED DESCRIPTION OF THE INVENTION

[0085] PCT Application No. WO98/41266 filed by Joe Fisher (WO98/41266)teaches a method of accelerating the resuscitation of a patient whichhas been anaesthetized by providing the patient with a flow of fresh gas(FGF) and a source of reserve gas is expressly incorporated herein byreference. As thought in WO98/41266, when the patient breathes at a rateless than or equal to the fresh gas flowing into the circuit, all of theinhaled gas is made up of fresh gas. When the patient's minuteventilation exceeds the fresh gas flow, the inhaled gas is made up ofall of the fresh gas and the additional gas is provided by “reserve gas”with a composition similar to the fresh gas but with CO₂ added such thatthe concentration of CO₂ in the reserve gas of about 6% is such that itspartial pressure is equal to the partial pressure of CO₂ in the mixedvenous blood. At no time while using this method will the patientrebreathe gas containing anaesthetic. In order to accelerate theresuscitation of the patient, a source of fresh gas is provided fornormal levels of minute ventilation, typically 5 L per minute and asupply of reserve gas is provided for levels of ventilation above 5 Lper minute wherein the source of reserve gas includes approximately 6%carbon dioxide having a PCO₂ level substantially equal to that of mixedvenous blood.

[0086] Although Fisher's WO98/41266 method prevents significantvariations in P_(ET)CO₂, it cannot keep PCO₂ precisely constant as aresult of two imperial approximations in the method:

[0087] a) Setting FGF equal to the baseline minute ventilation as Fishertaught is excessive to keep the PaCO₂ from decreasing, since withincreased ventilation, fresh gas from the anatomic dead space enters thealveoli providing increased alveolar ventilation which tends to lowerPaCO₂.

[0088] b) Setting PrgCO₂ substantially equal to PvCO₂ prevents theelimination of CO₂ and tends to increase PaCO₂ towards PrgCO₂ asventilation increases.

[0089] The proof assumes the same circuit described by Fisher, where aflow of fresh gas with a PCO₂ of 0 is set equal to Verest, and thebalance of V_(E) consists of reserve gas with a PCO₂ of PrgCO₂. Thisproof will show that PrgCO₂ should be equal to PaCO₂, and not to PvCO₂as previously approximated in order for P_(ET)CO₂ to remain constant forany increase in V_(E).

[0090] In pending application (Fisher I A, Vessely A., Sasano H.,Volyesi G., Tesler J.: entitled Improved Rebreathing Circuit forMaintaining Isocapnia), filed in Canada March 2000 and in the USA inOctober 2000 as Ser. No. 09/676,899, the disclosure of which isexpressly incorporated herein by reference) there is described a methodof simplifying the circuit taught by Fisher (WO98/41266), wherein thereserve gas may be replaced by previously exhaled gas. The first filedFisher application teaches that the fresh gas flow is set equal tominute ventilation to prevent change in P_(ET)CO₂ and PaCO₂. This is notoptimal to prevent changes P_(ET)CO₂ and PaCO₂ since as minuteventilation increases, the fresh gas previously residing in the tracheaexhaled without engaging in gas exchange can then be inhaled into thealveoli and hence adds to gas exchange and thus P_(ET)CO₂ and PaCO₂which will equilibrate to a valve lower than those at rest.

[0091] However, the present invention teaches that to prevent changes inP_(ET)CO₂ and PaCO₂ the fresh gas flow should be substantially equal tothe baseline ventilation minus the anatomic dead space ventilation.

[0092] Pending Canadian application Serial No. 2,340,511 filed by Fisheron Mar. 31, 2000 entitled A Portable Partial Rebreathing Circuit to Setand Stabilize End Tidal and Arterial PCO₂ Despite Varying Levels ofMinute Ventilation which is also incorporated herein by referencedescribes a circuit a circuit that exploits the same principle inmaintaining PCO₂ constant; however, it replaces the fresh gas reservoirbag with a substantially flexible container which is actively collapsedby the inspiratory effort of the patient during inspiration andpassively expands during expiration drawing into itself and the circuitatmospheric air through a port provided for that purpose. The expiratoryreservoir is provided with a flexible bag so that the volume of expiredgas rebreathed is displaced by collapse of the bag rather thanentrainment of atmospheric air, thus preventing the dilution of CO₂ inthe expired gas reservoir.

[0093] It is the primary object of the present invention to form aportable circuit to reap the benefits of controlling the PCO₂ at aconstant level and not having to incur the expense and inconvenience ofsupplying fresh gas. Furthermore the compact nature of the presentinvention will make its use practical outdoors, during physical activityand in remote environments, for example, for the resuscitation ofnewborns with air yet preventing an excessive decrease in PCO₂. In theprior art Fisher teaches that the total fresh gas flow into the bellowsshould be equal to minute ventilation. This again is not optimal toprevent changes P_(ET)CO₂ and PaCO₂ since as minute ventilationincreases, the fresh gas previously residing in the trachea exhaledwithout an opportunity to engage in gas exchange can now be inhaled intothe alveoli and add to gas exchange and thus P_(ET)CO₂ and PaCO₂ willequilibrate to a value lower than those at rest.

[0094]FIG. 1 shows a non-rebreathing circuit. In FIG. 1, anon-rebreathing valve 10 is connected distally to two ports 11 and 12.The port 12 is connected in parallel to a source of fresh gas 13 (whichdoes not contain CO₂) and a fresh gas reservoir 14. A one-way pressurerelief valve 15 prevents overfilling of the reservoir 14 by ventingexcess fresh gas. The port 11 is connected via a one-way valve 16 to asource of gas (containing CO₂) whose PCO₂ is equal approximately to thatof the arterial PCO₂. The source of gas is called the reserve gas anddenoted by a reference numeral 17. The non-rebreathing valve 10 isfurther connected to an exit port 18, from which the subject or thepatient breathes.

[0095]FIG. 5 depicts schematic representations of a lung atprogressively increasing ventilation (A-D). Gas in the alveolarcompartment of the lung participates in gas exchange, and thus cancontribute to the elimination of CO₂, whereas gas in the anatomical deadspace does not contribute to gas exchange. The hatched area indicatesfresh gas; the stippled area indicates reserve gas.

[0096] V_(E) is the total amount of gas ventilation the lung, includingboth the alveolar compartment and the anatomical dead space. V_(D)an isthe amount of gas ventilating just the anatomical dead space. Therefore,V_(E)−V_(D)an is the amount of gas available for ventilating thealveolar compartment, i.e., the amount of gas which can contribute togas exchange (alveolar ventilation, V_(A)).

[0097] When V_(E)−V_(D)an is less than or equal to the fresh gas flow“FGF” from the source of fresh gas flow 13, only fresh gas(non-CO₂-containing gas) enters the alveolar compartment. WhenV_(E)−V_(D)an exceeds FGF, the reservoir 14 containing freshnon-CO₂-containing gas empties first and the balance of inhaled gas isdrawn from the reserve gas 17 which contains a specific concentration ofCO₂. If minute ventilation exceeds FGF, the difference between minuteventilation and fresh gas flow is made up of gas from the reserve gassource 17 which contains CO₂ at a partial pressure which, beingsubstantially the same as that in the arterial blood, eliminates anygradient for diffusion of CO₂ between the two compartments. For example,if the FGF is 3 L per minute and the subject breathes at 5 L per minuteor less, then the patient will inhale only non-CO₂-containing gas thatcomes from the source(s) of the fresh gas flow 13 and 14. In this case,a proportion of the fresh gas will ventilate the alveolar compartment(for example, at 4 L per minute) and the remainder of the fresh gas willventilate the anatomical dead space (for example, at 1 L/min). ThusV_(E)−V_(D)an establishes the maximum potential alveolar ventilation(V_(A)).

[0098] When FGF is set exactly equal to V_(E)−V_(D)an (FIG. 5, panel C),fresh gas, and only fresh gas provides all the V_(A). Therefore anyincrease in ventilation will result in reserve gas being the onlyadditional gas drawn into the alveolar compartment. To set the FGF,after first approximately matching the fresh gas flow to V_(E), the FGFcan be slowly decreased, for example, in 200 mL/min decrements, withoutaffecting the PaCO₂ (FIG. 8). This is because the initial decreases inFGF decrease only the amount of FGF ventilating the anatomical deadspace, but not the alveolar compartment. At a certain point, which weterm the “inflection point”, any further decrease in FGF will decreasethe volume of fresh gas ventilating the alveolar compartment per unittime and PCO₂ will begin to rise exponentially. The inflection point isthe point at which FGF=V_(E)−V_(D)an, and represents the FGF required tomaintain PCO₂ constant.

[0099] Now considering the concentration of CO₂ which is required in thereserve gas in order to provide no ventilation. A mathematical model hasbeen used to calculate the PaCO₂ as a function of minute ventilation(FIG. 6). Note that for each FGF and PrgCO₂ tested, the PaCO₂, asventilation increases, approaches the PCO₂ of the reserve gas. Thisindicates that the appropriate reserve concentration is that equal tothe desired PaCO₂. (Curves 3 and 4). A system of equations belowconfirms that the reserve gas PCO₂ must be equal to the arterial PCO₂.

[0100] When ventilation approaches infinity, the PCO₂ of the gas in thealveoli will approach the PrgCO₂. Since the PaCO₂ (for example 40 mmHg)is in equilibrium with the alveolar PCO₂, the PaCO₂ will approach thePrgCO₂ which has been set at PvCO₂ (46 mmHg), and thus will not bemaintained at initial levels, for example 40 mmHg.

[0101] Clearly the PrgCO₂ cannot be set equal to PvCO₂. The presentinventors have determined the PrgCO₂ should instead be set equal toPaCO₂ in order to maintain PaCO₂ unchanged at all levels of V_(E) aboveresting V_(E) (testing V_(E)). Although Fisher's method works well atlow V_(E), the present invention offer the following improvement whichworks well at all V_(E), and in so doing provide a better explanation ofthe underlying physiology.

[0102] FGF shall equal resting minute ventilation minus anatomical deadspace ventilation (V_(E)−V_(Dan)).

[0103] This proof assumes the same circuit described by Fisher, where aflow of fresh gas with a PCO₂ of 0 is set equal to V_(E)rest, and thebalance of V_(E) consists of reserve gas with a PCO₂ Of PrgCO₂. Thisproof will show that PrgCO₂ should be equal to PaCO₂, and not to PvCO₂as previously approximated in order for P_(ET)CO₂ to remain constant forany increase in V_(E).

[0104] In the above and following description,

[0105] P_(ET)CO₂ is defined as the end tidal partial pressure of carbondioxide (mmHg);

[0106] Prest_(ET)CO₂ is the end tidal pressure of carbon dioxide (mmHg);

[0107] PiCO₂ is the inspired partial pressure of carbon dioxide (mmHg);

[0108] Pbar is the barometric pressure (mmHg);

[0109] V_(E) is the minute ventilation (mL/min);

[0110] VCO₂ is the volume of CO₂ produced in 1 minute (mL/min);

[0111] VrestCO₂ is the volume of CO₂ produced at rest in 1 minute(mL/min);

[0112] Verest is the minute ventilation at rest;

[0113] n is the minute ventilation expressed as number of times minuteventilation at rest;

n is equal to V_(E)/V_(E)rest, so that V _(E) =n*V _(E) rest  (1)

[0114] By specifying that VCO₂ remains at VrestCO₂, so thatVCO₂=VrestCO₂; and P_(ET)CO₂ remains at Prest_(ET)CO₂, so thatP_(ET)CO₂=Prest_(ET)CO₂.

[0115] The difference between the inspired and expired PCO₂ (as afraction of the barometric pressure) times the ventilation must be equalto the CO₂ produced by the body in a given period of time (for example 1minute).

(Prest _(ET) CO ₂ −PiCO ₂)/Pbar*V _(E) =VrestCO ₂  (2)

[0116] With Fisher's circuit, inspired PCO₂ can be calculated for any n.The inspired PCO₂ is an average of the PCO₂ of the fresh gas (0 mmhg)and the reserve gas (PrgCO₂), weighted by the relative volumes inspired:

PCO ₂=(n−1)/n*PrgCO ₂  (3)

[0117] For example, at 4×V_(E)rest, inspired PCO₂ is ¾ reserve gas PCO₂,because reserve gas comprises ¾ of the total gas inspired, while theremaining ¼ is fresh gas which has a PCO₂ of 0.

[0118] Substitution of 1 and 3 into 2 gives

((P _(ET) CO ₂−(n−1)/n*PrgCO ₂)/Pbar)*n*V _(E) rest=VrestCO ₂)

[0119] Solving for PrgCO₂,

P _(ET) CO ₂=(n−1)/n*PrgCO ₂ =VrestCO ₂ *pbar/(n*V _(E) rest)

P _(ET) CO ₂ −VrestCO ₂ *Pbar/(n*V _(E) rest)=(n−1)/n*prgCO ₂

(P _(ET) CO ₂ −VrestCO ₂ *Pbar/(n*V _(E) rest))*n/(n−1)=PrgCO ₂

PrgCO ₂=(Prest _(ET) CO ₂ −VrestCO ₂ *Pbar/(n*Vrest))*n/(n−1)  (4)

Now,

(VCO ₂ /V _(E))*Pbar=Prest _(ET) CO ₂  (5)

[0120] Solving (5) for V_(E), we obtain

V _(E) =VCO ₂ *Pbar/Prest _(ET) CO ₂  (6)

[0121] Then at V_(E)rest,

Verest=VrestCO ₂ *Pbar/Prest _(ET) CO ₂  (7)

[0122] Substituting 7 into 4, we obtain,

PrgCO ₂=(Prest _(ET) CO ₂ VrestCO ₂ *Pbar/(n*(VrestCO ₂ *Pbar/Prest_(ET) CO ₂))*n/(−1)  (8)

[0123] Canceling like terms for numerator and denominator in 8, weobtain

PrgCO ₂=(Prest _(ET) CO ₂ −Prest _(ET) CO ₂ /n)*n/(n−1)  (9)

[0124] Factoring out Prest_(ET)CO₂ in (9), we obtain

PrgCO ₂ =Prest _(ET) CO ₂*(1−1/n)*n/(n−1)  (10)

[0125] Factoring out n in (10), we obtain

PrgCO ₂ =Prest _(ET) CO ₂*((n−1)/n)*n/(n−1)  (11)

[0126] Cancelling like terms from (11),

PrgCO₂=Prest_(ET)CO₂  (12)

[0127] Therefore, the reserve gas PCO₂ must be equal to the restingend-tidal PCO₂ in order for the condition to be met of end-tidal PCO₂remaining constant with increased V_(E).

[0128] This provides an additional advantage over Fisher's method,because the resting P_(ET)CO₂ can be obtained more readily than thePvCO₂. To maintain P_(ET)CO₂ constant, the PrgCO₂ can be set by simplymeasuring the concentration of CO₂ in gas sampled at end-expiration. Ifthis is unknown, the PrgCO₂ can be set equal to the desired PaCO₂ (forexample 40 mmHg). With higher and higher minute ventilation, thesubject's PaCO₂ will approach the PrgCO₂, whatever it might have beeninitially. In this situation, preferably, the fresh gas flow would alsobe set equal to the required alveolar ventilation which would producethe desired arterial PCO₂. This could be empirically determined, orcalculated from the alveolar gas equation.

[0129] Therefore, from the above it is shown that in order to make PaCO₂independent of minute ventilation (FIG. 6), FGF should be setsubstantially equal to baseline minute ventilation minus anatomical deadspace, and reserve gas PCO₂ should be set substantially equal toarterial PCO₂.

[0130] The present invention provides a new equation more fully andaccurately describing what is happening than that of Fisher. PvCO₂ inFisher's equation has been replaced with PaCO₂. V_(E) in Fisher'sequation has been replaced with V_(E)−V_(Dan). Finally, an additionalterm has been added which describes the effect of the alveolar deadspace. The alveolar dead space ventilation has the effect of decreasingthe amount of fresh gas and reserve gas by the proportion of totalventilation of the alveolar compartment which it occupies.$V_{A} = \left. {\overset{\_}{1}\frac{V_{D_{a|V}}}{V_{E} - V_{Dan}}\quad }\leftrightarrow{{FGF} + \left( {\left( {V_{E} - V_{Dan}} \right) - {FGF}} \right)}\leftrightarrow{\frac{{- {{Pa}{CO}}_{2}} - {{Prg}{CO}}_{2}}{{{Pa}{CO}}_{2}}} \right.$

[0131]FIG. 2 shows the schematic of the standard anaesthetic circlecircuit, spontaneous ventilation. When the patient exhales, theinspiratory valve 21 closes, the expiratory valve 22 opens and gas flowsthrough the corrugated tubing making up the expiratory limb of thecircuit 23 into the rebreathing bag 24. When the rebreathing bag 24 isfull, the airway pressure-limiting (APL) valve 25 opens and the balanceof expired gas exits through the APL valve 25 into a gas scavenger (notshown). When the patient inhales, the negative pressure in the circuitcloses the expiratory valve 22, opens the inspiratory valve 21, anddirects gas to flow through the corrugated tube making up theinspiratory limb of the circuit 26. Inspiration draws all of the gasfrom the fresh gas hose 27 and makes up the balance of the volume of thebreath by drawing gas from the rebreathing bag 24. The gas from therebreathing bag contains expired gas with CO₂ in it. The CO₂ isextracted as the gas passes through the CO₂ absorber 28 and thus isdelivered to the patient (P) without CO₂ (but still containing exhaledanaesthetic vapor, if any).

[0132] A modification of the circuit as shown in FIG. 2 to allowhyperventilation of patient under anaesthesia is shown in FIG. 3.

[0133] The modification comprises:

[0134] 1. A circuit which acts functionally like a standard selfinflating bag (such as made by Laerdal), having:

[0135] a) a non-rebreathing valve 29, such as valve #560200 made byLaerdal, that functions during spontaneous breathing as well as manuallyassisted breathing;

[0136] b) an expired gas manifold 30, such as the expiratory deviator#850500, to collect expired gas and direct it to a gas scavenger system(not shown) or to the expiratory limb of the anaesthetic circuit (FIG.4);

[0137] c) a self inflating bag 31 whose entrance is guarded by a one-wayvalve 32 directing gas into the self inflating bag 31.

[0138] 2. A source of fresh gas (i.e., not containing vapor) 33 e.g.oxygen or oxygen plus nitrous oxide with a flow meter (32).

[0139] 3. A manifold 34 with 4 ports:

[0140] a) port 35 for input of fresh gas 33;

[0141] b) port 36 for a fresh gas reservoir bag 37;

[0142] c) port which is attached a one-way inflow valve 38 that openswhen the pressure inside the manifold is 5 cm H₂O less than atmosphericpressure, such as Livingston Health Care Services part #9005, (assuringthat all of the fresh gas is utilized before opening);

[0143] d) a bag of gas 39 whose PCO₂ is equal to approximately to thatof the arterial PCO₂ connected to inflow valve 38 (alternatively, thevalve and gas reservoir bag can be replaced by a demand regulator, suchas Lifetronix MS91120012, similar to that used in SCUBA diving, and acylinder of compressed gas);

[0144] e) a port to which a one-way outflow valve 40, such as LivingstonHealth Care Services catalog part #9005, that allows release of gas fromthe manifold to atmosphere when the pressure in the manifold is greaterthan 5 cm H₂O.

[0145] The operation method of the anaesthetic circuit is shown as FIG.4A. The distal end of the nonrebreathing valve 29 (Laerdal type) asshown in FIG. 3 is attached to the patient.

[0146] The proximal port of the nonrebreathing valve 39 is attached to a3 way respiratory valve 41 which can direct inspiratory gas either fromthe circle anaesthetic circuit (FIG. 4B) or from the new circuit (FIG.4C). The expiratory manifold 30 of the self inflating bag's nonrebreathing valve 29 is attached to the expiratory limb of theanaesthetic circuit 23. Regardless of the source of inspired gas,exhalation is directed into the expiratory limb of the anaestheticcircuit.

[0147] To maximize the elimination of anesthetic vapor from thepatient's lung, the 3-way respiratory stopcock 41 is turned such thatthe patient inspiration is from the new circuit (FIG. 4C). Thus inspiredgas from the very first breath after turning the 3-way valve onwardcontains no vapor, providing the maximum gradient for anaesthetic vaporelimination.

[0148] An increased breathing rate will further enhance the eliminationof vapor from the lung. If breathing spontaneously, the patient can bestimulated to increase his minute ventilation by lowering the FGF 42thereby allowing PCO₂ to rise. Using this approach the PCO₂ will riseand plateau independent of the rate of breathing, resulting in aconstant breathing stimulus. All of the ventilation is effective ineliminating vapor.

[0149] If the patient is undergoing controlled ventilation, he can alsobe hyperventilated with the self-inflating bag 31. In either case, thepatient's PCO₂ will be determined by the FGF 42. As long as the FGFremains constant, the PCO₂ will remain constant independent of theminute ventilation.

[0150] Conventional servo-controlled techniques designed to preventchanges in PCO₂ with hyperpnea are less affected by changes in CO₂production than the circuit; however, they have other limitations. Theassumption that detected changes in P_(ET)CO₂ are due to a change inPaCO₂ is not always warranted 34. Small changes in ventilatory patterncan “uncouple” P_(ET)CO₂ from PaCO₂, resulting in P_(ET)CO₂ being aninappropriate input for the control of PaCO₂. For example, a smallerV_(T) decreases V_(A) (which tends to increase PaCO₂) but will alsodecrease P_(ET)CO₂, causing a servo-controller to respond with aninappropriate increase in inspired CO₂. Even under ideal conditions, aservo-controlled system attempting to correct for changes in P_(ET)CO₂cannot predict the size of an impending V_(T) in a spontaneouslybreathing subjecting and thus deliver the appropriate CO₂ load. If in anattempt to obtain fine control the gain in a servo-control system is settoo high, the response becomes unstable and may result in oscillation ofthe control variable 31. Conversely, if the gain is set too low,compensation lags 39. Over-damping of the signal results in the responsenever reaching the target. To address these problems, servo-controllersrequire complex algorithms 36 and expensive equipment.

[0151] When CO₂ production is constant, the circuit has the theoreticaladvantage over servo-controlled systems in that it provides passivecompensation for changes in V. This minimizes changes in V_(A),pre-emptying the need for subsequent compensation. Maintenance of anearly constant V_(A) occurs even during irregular breathing, includingbrief periods when V is less than the FGF. Under this circumstance,excess FGF is stored in the fresh gas reservoir and subsequentlycontributes to V_(A) when ventilation exceeds FGF.

[0152] When CO₂ production increases during hyperventilation, as wouldoccur with increased work of breathing or exercise, our method requiresmodification. To compensate, additional V_(A) can be provided either byincreasing FGF or by lowering the PCO₂ of the reserve gas below thePvCO₂.

[0153] As such, a simple circuit that disassociates V_(A) from V hasbeen described. It passively minimizes increases in VA that wouldnormally accompany hyperventilation when CO₂ production is constant. Itcan be modified to compensate for increases in CO₂ production. Thecircuit may form the basis for a simple and inexpensive alternative toservo-controlled systems for research and may have therapeuticapplications.

[0154] Referring to FIG. 7, the patient breathes through one port of aY-piece 71. The other 2 arms of the Y-piece contain 1-way valves. Theinspiratory limb of the Y-piece contains a one-way valve, theinspiratory valve 72 which directs gas to flow towards the patient whenthe patient makes an inspiratory effort, and acts as a check valvepreventing flow in the opposite direction during exhalation. The otherlimb of the Y-piece 71, the expiratory limb, contains a one-way valve,the expiratory valve 73, positioned such that it allows gas to exit theY-piece 71 when the patient exhales, and also acts as a check valve toprevent flow towards the patient when the patient inhales. Immediatelydistal to the expiratory limb of the Y-piece is attached large boretubing 74, termed “reservoir tube” that is open at its distal end 75.The reservoir tube is preferably greater then 22 mm in diameter, and itslength is such that the total volume of the tubing is about or greaterthan 3 L when it is being used for an average (70 kg) adult. Largervolumes of reservoir tubing will be required for larger subjects andvice versa. The inspiratory port is connected to a source of fresh gas76, i.e., gas not containing CO₂, flowing into the circuit at a fixedrate and a fresh gas reservoir bag 79 of about 3 L in volume. A bypassconduit 77 connects the expiratory limb and the inspiratory limb. Theopening of the conduit to the expiratory limb is preferably as close aspossible to the expiratory one-way valve. This conduit contains aone-way valve 78 allowing flow from the expiratory to the inspiratorylimb. The conduit's one-way valve 78 allowing flow from the expiratoryto the inspiratory limb. The conduit's one-way valve 78 requires anopening pressure differential across the valve slightly greater thanthat of the inspiratory valve. In this way, during inspiration, freshgas, consisting of fresh gas flow and the contents of the fresh gasreservoir bag, is preferentially drawn from the inspiratory manifold.

[0155] When the patient's minute ventilation less anatomical dead spaceis equal to or less than the FGF, only fresh gas (FG) is breathed.During exhalation FG accumulates in the FG reservoir. During inhalationfresh gas glowing into the circuit and the contents of the fresh gasreservoir are inhaled. When minute ventilation less anatomical deadspace exceeds FGF, on each breath, FG is breathed until the FG reservoiris emptied. Additional inspiratory efforts result in a decrease inpressure on the inspiratory side of the current. When this pressuredifferential across the valve of the bypass conduit exceed its openingpressure, the one-way valve opens and exhaled gas is drawn back from theexpired gas reservoir into the inspiratory limb of the Y-piece and henceto the patient. The last gas to be exhaled during the previous breath,termed “alveolar gas” is the first to be drawn back into the inspiratorylimb and inhaled (rebreathed) by the subject.

[0156] A method of measuring the anatomical dead space can be provided.The fresh gas flow can be set equal to the minute ventilation less theanatomical dead space ventilation V_(Dan). Fresh gas flow shouldinitially be set approximately equal to the resting minute ventilation.Fresh gas flow can be slowly decreased, for example, 200 mL/min at atime. P_(ET)CO₂, will remain flat initially, and at some point willbegin to rise exponentially. This can be seen in FIG. 8, in which ahuman subject breathes through the circuit while fresh gas flow wasdecreased in steps. This point is defined as the “inflection point”. TheFGF at the inflection point is equal to V_(E)−V_(D)an. It is apparentthat this circuit can therefore be used to measure anatomical dead spaceas the difference between resting ventilation and the inflection point,divided by the respiratory frequency V_(Dan)=(V_(E)−VFGF at inflectionpoint), and anatomical dead space=(V_(E)-FGF at inflection point)/f.Those skilled in the art will recognize that there are other ways to usethis circuit to measure dead space for example measuring the restingV_(E) and P_(ET)CO₂, asking the subject to hyperventilate and thenprogressively decreasing the fresh gas glow until resting P_(ET)CO₂ isreached. Because the rebreathing circuit taught by Fisher works in thesame way, it too can be used to measure anatomical dead space in thisway. Other variations of using these circuits to measure anatomical deadspace will be apparent to those skilled in the art. This method ofmeasuring anatomical dead space can be used with any circuit where freshgas flow limits alveolar ventilation under the conditions where allfresh gas flow is inhaled during breathing.

[0157]FIG. 9 shows a portable isocapna circuit. The patient or subjectbreathes (inhales and exhales) through one port of a Y-piece 91. Theisocapnia circuit has another two ports in a form of two limbs of theY-piece 91, and each of them comprises a one-way valve. One of the limbswith an inspiratory valve 92 functions as an inspiration port, while theother limb with an expiratory valve 93 functions as an expiration port.The inspiratory valve 92 directs gas to flow towards the patient whenthe patient makes an inspiratory effort, and acts as a check valvepreventing flow in the opposite direction during exhalation. Theexpiratory valve 93 allows gas to exit the Y-piece 91 when the patientexhales, and also acts as a check valve to prevent flow towards thepatient when the patient inhales. Immediately distal to the expiratorylimb of the Y-piece 91, a large bore tubing termed “alveolar gasreservoir” 94 is attached. The alveolar gas reservoir 94 is contained ina pliable bag of about 3 L in volume. Bag 95, has a proximal end sealedaround a proximal end of the alveolar gas reservoir 94. The expiratorygas reservoir bag 95 further has another tubing called the “exhausttubing” 96 situated at a distal end where the expired gas exits toatmosphere 97. Thus arranged, most of the exhaust tubing 96 is containedin the expiratory gas reservoir bag 95, and which is sealed to thecircumference of the exhaust tubing 96 at its distal end. Preferably,the exhaust tubing 96 has a diameter smaller than that of the alveolargas reservoir 94. In one embodiment, the alveolar gas reservoir 94 isabout 35 mm in diameter, and has a length to provide a total volume ofabout or greater than 0.3 while being applied to an average (70 kg)adult. Distal to the expiratory limb of the Y-piece 91, a large boretubing termed “alveolar gas reservoir” 94 is attached. The alveolar gasreservoir 94 is contained in a pliable bag of about 3 L in volume. Thepliable bag, named “expiratory gas reservoir bag” 95, has a proximal endsealed around a proximal end of the alveolar gas reservoir 94. Theexpiratory gas reservoir bag 95 further has another tubing called the“exhaust tubing” 96 situated at a distal end where the expired gas exitsto atmosphere 97. Thus arranged, most of the exhaust tubing 96 iscontained in the expiratory gas reservoir bag 95, and which is sealed tothe circumference of the exhaust tubing 96 at its distal end.Preferably, the exhaust tubing 96 has a diameter smaller than that ofthe alveolar gas reservoir 94. In one embodiment, the alveolar gasreservoir 94 is about 35 mm in diameter, and has a length to provide atotal volume of about or greater than 0.3 while being applied to anaverage (70 kg) adult.

[0158] The inspiratory limb opens into a cylindrical containercomprising a rigid proximal end plate 98, a collapsible plicate tube 99extending distally from the circumference of the proximate end plate 98,and a distal end rigid plate 110 sealing the distal end of thecollapsible plicate tube 99. When not in use, the collapsible plicatetube 99 is kept open by the gravitation of the distal end rigid plate110, and/or by the force of a spring 111 attached on the collapsibleplicate tube 99, and/or by intrinsic recoil of the plicate tubing 99.The inspiratory limb is also open to the atmosphere by means of a nozzle112, to which a tube 113 is attached. The rigid plate 110 is open to anozzle 114, to which another tube 115 is attached. The proximal endplate 98 has a protuberance 116 pointing at the tube 115 that is alignedwith the internal opening of the distal end plate nozzle 114. Thecombination of the proximal end plate 98, the collapsible plicate tube99, the distal end rigid plate 110, the spring 111, the inspiratory limbnozzle 112, the tube 113 attached to the nozzle 112, the distal endplate nozzle 114, the tube 115 attached to the distal end plate nozzle114 and the protuberance 116 are in aggregate as am “atmosphere airaspirator (AAA)”. A bypass conduit 117 is further included in theY-piece 91 to connect the expiratory limb and the inspiratory limb. Theopening of the bypass conduit 117 is preferably as close as possible tothe expiratory valve 93. The bypass conduit 117 has a one-way valve 118allowing flow from the expiratory limb to the inspiratory limb only. Theone-way valve 118 of the bypass conduit 117 requires an opening pressuredifferential slightly greater than the pressure difference between theinspiratory limb pressure and atmospheric pressure that is sufficient tocollapse the plicate tube 99. In this way, during inspiration,atmosphere air contained in the atmospheric air aspirator and the airbeing continuously aspirated into the inspiratory limb is preferentiallydrawn from the inspiratory manifold.

[0159] Considering the above isocapnia circuit without the spring 111,the nozzle 114 on the distal end plate 114, or the internally directedprotuberance 116, each inspiration drawn initially from the atmosphericair aspirator collapses the plicate tube 99 and approximates the distalend plate 110 to the proximal end plate 18 when the patient begins tobreathe. As long as the plicate tube 99 is partially collapsed, there isa constant sub-atmospheric pressure in the inspiratory limb of theisocapnia circuit. The sub-atmospheric pressure creates a pressuregradient that draws the atmospheric air into the inspiratory limb of theisocapnia circuit through the nozzle 112 and the tube 113. When theminute ventilation of the subject is equal to or less than the intendedflow of atmospheric air into the aspirator, only atmospheric air isbreathed. During exhalation, atmospheric air accumulates in theaspirator. During inhalation, inspired gas consist of the contents ofthe atmospheric air aspirator and the atmospheric air flowing into theinspiratory limb through the nozzle 113. When the minute ventilation ofthe subject exceeds the net flow of the atmospheric air into theisocapnia circuit, air is breathed for each breath until the atmosphericair aspirator is collapsed. Additional inspiratory efforts result in anadditional decrease in gas pressure on the inspiratory side of theisocapnia circuit.

[0160] When the pressure differential across the valve 118 of the bypassconduit 117 exceeds its opening pressure, the one-way valve 118 opensand the exhaled gas is drawn back from the expiratory reservoir bag 95into the inspiratory limb of the Y-piece 91 and hence to the patient. Tothe extent that the opening pressure of the valve 118 is close to thepressure generated by the recoil of the atmospheric air aspirator, therewill be little change in the flow of atmospheric air into the isocapniacircuit during inspiration after the atmospheric air aspirator hascollapsed. The last gas to be exhaled during the previous breath, termed“alveolar gas”, is retained in the alveolar gas reservoir 14 and is thefirst gas to be drawn back into the inspiratory limb of the isocapniacircuit and inhaled (rebreathed) by the patient. After several breaths,the rest of the expired gas from the expiratory gas reservoir bag 95contains mixed expired gas. The mixed expired gas from the expiratorygas reservoir bag 95 replace the gas drawn from the alveolar gasreservoir 94 and provides the balance of the inspired volume required tomeet the inspiratory effort of the patient. The greater restriction inthe diameter of the second tube, that is, the exhaust tubing 96, than inthe alveolar gas reservoir 94 results in the gas being drawn into thealveolar gas reservoir 94 being displaced by the collapse of theexpiratory gas reservoir bag 95 in preference to drawing air from theambient atmosphere. The exhaust tubing in the expiratory reservoir bag96 provides a rout for exhaust of expired gas and acts as a reservoirfor that volume of atmospheric air diffusing into the expiratoryreservoir bag through the distal opening, tending to keep suchatmospheric air separate from the mixed expired gas contained in theexpiratory gas reservoir bag 95.

[0161] During exhalation and all of inhalation until the collapse of theatmospheric gas aspirator, the flow of atmospheric air into the circuitwill remain constant. However, after the atmospheric air aspiratorcollapses the pressure gradient will increase. The effect of theincrease in total flow will depend on the difference between the openingpressure of the bypass valve 118 and the recoil pressure of theatmospheric air aspirator times the fraction of the respiratory cyclewhen the atmospheric air aspirator is collapsed. If the fraction of therespiratory cycle when the atmospheric air aspirator is collapsed isgreat, as when there is a very great excess minute ventilation above therate of atmospheric air aspiration, the atmospheric air aspirator can bemodified adding a second port for air entry at, for example, the distalend plate nozzle 114. As a result, the total flow from the two portsprovides the desired total flow of air into the circuit under the recoilpressure of the atmospheric air aspirator. When the atmospheric airaspirator collapses on inspiration, the second port 114 is occluded bythe protuberance 116. The remaining port, that is, the nozzle 112,provides a greater resistance to air flow to offset the greater pressuregradient being that gradient required to open the bypass valve 118.

[0162] In the above embodiment, it is assumed that the gravitationacting on the distal plate 110 provides the recoil pressure to open theatmospheric air aspirator. The disadvantage to this configuration isthat the distal end plate 110 must be heavy enough to generate thesub-atmospheric pressure. This may be too heavy to be supported byattachment to a face mask strapped to the face. Furthermore, movementsuch as walking or running or spasmodic inhalation will cause variationsin the pressure inside the atmospheric air aspirator and hence variationin flow of air into the atmospheric air aspirator. In such cases, it isbetter to minimize the mass of the distal end plate 110 and use adifferent type of motive force to provide recoil symbolized by thespring 111.

[0163] Preferably the circuit as described above is installed in a caseto render it fully portable. The case may include the appropriate numberof capped ports to allow proper set up and use of the circuit.

[0164] Other embodiments of the invention will appear to those skilledin the art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples to be considered as exemplary only, with a true scope andspirit of the invention being indicated by the following claims.

1. A method of maintain PCO₂ constant, comprising setting a fresh gasflow equal to baseline minute ventilation minus anatomical dead spaceventilation.
 2. A method of maintain PCO₂ constant, comprising providinga reserve gas with a PCO₂ substantially equal to arterial PCO₂.
 3. Amethod of setting up a fresh gas flow equal to baseline minuteventilation minus anatomical dead space ventilation, comprising: havinga subject breating on a breathing circuit, providing a fresh gas flowequal to a baseline minute ventilation of the subject; graduallydecreasing the fresh gas flow provided to the breathing circuit with adecrement small enough to avoid affecting an arterial PCO₂ of thesubject; and obtaining an inflection point at which the arterial PCO₂suddenly rises exponential, and the inflection point reflecting thefresh gas flow equal to baseline minute ventilation minus anatomicaldead space.
 4. The method of claim 3, further comprising a step ofhaving the subject breathing on a rebreathing circuit.
 5. The method ofclaim 3, further comprising a step of having the subject breathing on anon-rebreathing circuit.
 6. The method of claim 3, further comprising astep of having the subject breathing on a portable breathing circuit. 7.The method of claim 3, further comprising a step of gradually increasingthe fresh gas flow with a decrement of about 200 mL/minute.
 8. Themethod of claim 3, further comprising a step of obtaning the anatomicaldead space ventilation by substracting the baseline minute ventilationwith the fresh gas flow at the inflection point.
 9. A method to maintainisocapnia for a subject, comprising: providing the subject a fresh gasto the subject when the subject breathes at a rate less than or equal tothe fresh gas flowing to the subject, wherein fresh gas flow is equal toa baseline minute ventilation minus a dead space gas ventilation of thesubject; and providing the subject the fresh gas and a reserve gas whenthe subject breathes at a rate more than the fresh gas flowing to thesubject.
 10. The method of claim 9, wherein the reserve gas has apartial pressure of carbon dioxide equal to an arterial partial pressureof carbon dioxide of the subject.
 11. The method of claim 9, wherein thefresh gas provided to the subject contains a physiologicallyinsignificant amount of CO₂.
 12. An isocapnia circuit, comprising: anexit port, from which gases exit from the isocapnia circuit to apatient; a non-rebreathing valve, permitting gases delivered to the exitport for the patient, but preventing gases from passing therethrough tothe isocapnia circuit; a source of fresh gas, containing aphysiologically insignificant amount of CO₂ in communication with thenon-breathing valve to be delivered to the patient; a fresh gasreservoir, in communication with the source of fresh gas flow forreceiving excess fresh gas not breathed by the patient; and a reservegas supply, containing CO₂ having a PCO₂ approximately equal to PCO₂ inthe arterial blood of the patient provided to the patient to make upamount of gas required by the patient for breating that is not fulfilledfrom the gases delivered from the source of fresh gas and the fresh gasreservoir.
 13. The isocapnia circuit of claim 12, wherein the source ofgas, the fresh gas reservoir and the reserve gas supply are disposed ona side of the non-rebreathing valve remote from the exit port.
 14. Theisocapnia circuit of claim 12, further comprise a pressure relief incommunication with the source of fresh gas and the fresh gas reservoir.15. The isocapnia circuit of claim 12, wherein the reserve gas supplycomprises a demand valve regulator which opens when an additional gas isrequired by the patient, and closes when the additional gas is notrequired.